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The following is the listing of the Recommended Dietary Allowances (RDA), Adequate Intake (with asterisk), and Tolerable Upper Intake Level (ULs) according to the Institute of Medicine (IOM 2001). The Upper Intake Level refers to the maximum level likely to pose no threat of adverse effects.

Life Stage GroupRDA/AI*ULInfants
0-6 months
7-12 months(mg/day)
0.1*
0.3*(mg/day)
ND
NDChildren
1-3 yrs
4-8 yrs
0.5
0.6
30
40Males
9-13 yrs
14-18 yrs
19-50 yrs
50- >70 yrs
1.0
1.3
1.3
1.7
60
80
100
100Females
9-13 yrs
13-18 yrs
19-50 yrs
50- >70 yrs
1.0
1.2
1.3
1.5
60
80
100
100Pregnancy
<18 yrs
19-50 yrs
1.9
1.9
80
100Lactation
<18 yrs
19-50 yrs
2.0
2.0
80
100

Functions

Vitamin B6, in the form of pyridoxal phosphate, is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression. The primary role of vitamin B6, again performed by the active form pyridoxal phosphate, is to act as a coenzyme to many other enzymes in the body that are involved predominantly in metabolism. Pyridoxal phosphate generally serves as a coenzyme for many reactions and can help facilitate decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion reactions (Combs 2008).

Vitamin B6 is involved in the following metabolic processes:

  • Amino acid, glucose, and lipid metabolism
  • Neurotransmitter synthesis
  • Histamine synthesis
  • Hemoglobin synthesis and function
  • Gene expression

Amino acid metabolism

Pyridoxal phosphate is involved in almost all amino acid metabolism, from synthesis to breakdown.

  • Transamination. Transaminase enzymes needed to break down amino acids are dependent on the presence of pyridoxal phosphate. The proper activity of these enzymes are crucial for the process of moving amine groups from one amino acid to another.
  • Transsulfuration. Pyridoxal phosphate is a coenzyme needed for the proper function of the enzymes cystathionine synthase and cystathionase. These enzymes work to transform methionine into cysteine.
  • Selenoamino acid metabolism. Selenomethionine is the primary dietary form of selenium. Pyridoxal phosphate is needed as a cofactor for the enzymes that allow selenium to be used from the dietary form. Pyridoxal phosphate also plays a cofactor role in releasing selenium from selenohomocysteine to produce hydrogen selenide. This hydrogen selenide can then be used to incorporate selenium into selenoproteins (Combs 2008).
  • Conversion of tryptophan to niacin. Vitamin B6 is also required for the conversion of tryptophan to niacin and low vitamin B6 status will impair this conversion (Combs 2008).

PLP is also used to create physiologically active amines by decarboxylation of amino acids. Some notable examples of this include: histadine to histamine, tryptophan to serotonin, glutamate to GABA (gamma-aminobutyric acid), and dihydroxyphenylalanine to dopamine.

Gluconeogenesis

Vitamin B6 also plays a role in gluconeogenesis. Pyridoxal phosphate can catalyze transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis. Also, vitamin B6 is a required coenzyme of glycogen phosphorylase (Combs 2008), the enzyme that is necessary for glycogenolysis to occur.

Lipid metabolism

Vitamin B6 is an essential component of enzymes that facilitate the biosynthesis of sphingolipids (Combs 2008). Particularly, the synthesis of ceramide requires PLP. In this reaction, serine is decarboxylated and combined with palmitoyl-CoA to form sphinganine, which is combined with a fatty acyl CoA to form dihydroceramide. Dihydroceramide is then further desaturated to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B6 since S1P Lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP dependent.

Neurotransmitter, histamine, and hemoglobin synthesis

  • Neurotransmitters. Pyridoxal phosphate-dependent enzymes play a role in the biosynthesis of four important neurotranmsitters: serotonin, epinephrine, norepinephrine, and gamma-aminobutyric acid (Combs 2008).
  • Histamine. Pyridoxal phosphate is involved in the metabolism of histamine (Combs 2008).
  • Heme synthesis and hemoglobin action. Pyridoxal phosphate aids in the synthesis of heme and can also bind to two sites on hemoglobin to enhance the oxygen binding of hemoglobin (Combs 2008).

Gene expression

Pyridoxal phosphate has been implicated in increasing or decreasing the expression of certain genes. Increased intracellular levels of the vitamin will lead to a decrease in the transcription of glucocorticoid hormones. Also, vitamin B6 deficiency will lead to the increased expression of albumin mRNA. Also, pyridoxal phosphate will influence gene expression of glycoprotein IIb by interacting with various transcription factors. The result is inhibition of platelet aggregation (Combs 2008).

Deficiencies

Since many foods contain vitamin B6, severe vitamin B6 deficiency is rare (Brody 2004), although mild deficiencies are common, in spite of the low daily requirements (Turner and Frey 2005). A deficiency only of vitamin B6 is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B6 deficiency, as well as other micronutrient deficiencies (Bowman and Russell 2006). Since good sources are meats, fish, dairy, and eggs, one of the risk groups for deficiency are vegans, and a balanced vitamin B supplement is encouraged to prevent deficiency (Turner and Frey 2005). Those taking birth control pills also are a risk to have abnormally low levels (Turner and Frey 2005), as well as the taking of certain drugs (hydrolazine, penicillamine) or cases of particular genetic disorders (Brody 2004).

The classic clinical syndrome for B6 deficiency is a seborrheic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy (James et al. 2006).

While severe vitamin B6 deficiency results in dermatologic and neurologic changes, less severe cases present with metabolic lesions associated with insufficient activities of the coenzyme pyridoxal phosphate. The most prominent of the lesions is due to impaired tryptophan-niacin conversion. This can be detected based on urinary excretion of xanthurenic acid after an oral tryptophan load. Vitamin B6 deficiency can also result from impaired transsulfuration of methionine to cysteine. The pyridoxal phosphate-dependent transaminases and glycogen phosphorylase provide the vitamin with its role in gluconeogenesis, so deprivation of vitamin B6 results in impaired glucose tolerance (Combs 2008).

Toxicity

The Institute of Medicine (IOM 2001) notes that "No adverse effects associated with Vitamin B6 from food have been reported. This does not mean that there is no potential for adverse effects resulting from high intakes. Because data on the adverse effects of Vitamin B6 are limited, caution may be warranted. Sensory neuropathy has occurred from high intakes of supplemental forms."

Supplements that result in an overdose of pyridoxine can cause a temporary deadening of certain nerves such as the proprioceptory nerves, causing a feeling of disembodiment common with the loss of proprioception. This condition is reversible when supplementation is stopped (NIH 2008).

Because adverse effects have only been documented from vitamin B6 supplements and never from food sources, this article only discusses the safety of the supplemental form of vitamin B6 (pyridoxine). Although vitamin B6 is a water-soluble vitamin and is excreted in the urine, very high doses of pyridoxine over long periods of time may result in painful neurological symptoms known as sensory neuropathy. Symptoms include pain and numbness of the extremities, and in severe cases difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 milligrams (mg) per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day. In order to prevent sensory neuropathy in virtually all individuals, the Food and Nutrition Board of the Institute of Medicine set the tolerable upper intake level (UL) for pyridoxine at 100 mg/day for adults. Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the UL of 100 mg/day. Studies have shown, however, that in the case of individuals diagnosed with autism, high doses of vitamin B6 given with magnesium may be beneficial (Pfeiffer et al. 1998).

Preventive roles and therapeutic uses

Vitamin B6 is considered to have therapeutic uses in terms of having a calming effect on the nervous system and possibly alleviating insomnia by increasing serotonin levels in the brain. There also is evidence that vitamin B6 reduces nausea for some women who experience morning sickness, and does not have harmful impacts on the fetus. It also is used to decrease the risk of heart disease through lowering of homocysteine levels (Turner and Frey 2004).

At least one preliminary study has found that this vitamin may increase dream vividness or the ability to recall dreams. It is thought that this effect may be due to the role this vitamin plays in the conversion of tryptophan to serotonin (Ebben et al. 2002).

Nutritional supplementation with high dose vitamin B6 and magnesium is claimed to alleviate the symptoms of autism and is one of the most popular complementary and alternative medicine choices for autism. Three small randomized controlled trials have studied this therapy; the smallest one (with 8 individuals) found improved verbal IQ in the treatment group and the other two (with 10 and 15 individuals, respectively) found no significant difference. The short-term side effects seem to be mild, but there may be significant long-term side effects of peripheral neuropathy (Angley et al. 2007). Some studies suggest that the B6-magnesium combination can also help attention deficit disorder, citing improvements in hyperactivity, hyperemotivity/aggressiveness, and improved school attention (Mousain-Bosc et al. 2006).

References

  • Angley, M., S. Semple, C. Hewton, F. Paterson, and R. McKinnon. 2007. Children and autism. Part 2: Management with complimentary medicines and dietary interventions. Aust Fam Physician 36(10): 827-30. PMID 17925903. Retrieved December 11, 2008.
  • Bender, D. A., and A. E. Bender. 2005. A Dictionary of Food and Nutrition. New York: Oxford University Press. ISBN 0198609612.
  • Bowman, B. A., and R. M. Russell. Present Knowledge in Nutrition, 9th Edition. Washington, DC: International Life Sciences Institute. ISBN 9781578811984.
  • Brody, T. 2004. Vitamin B6 deficiency. Pages 3513-3515 in J. L. Longe, The Gale Encyclopedia of Medicine, volume 5. Detroit: Gale Grou/Thomson Learning. ISBN 0787654949.
  • Combs, G. F. 2008. The Vitamins: Fundamental Aspects in Nutrition and Health. San Diego: Elsevier. ISBN 9780121834937.
  • Ebben, M., A. Lequerica, and A. Spielman. 2002. Effects of pyridoxine on dreaming: A preliminary study. Perceptual & Motor Skills 94(1): 135-140.
  • Institute of Medicine (IOM) of the National Academies, Food and Nutrition Board. 2001. Daily Reference Intakes: Vitamins. National Academy of Sciences. Retrieved December 11, 2008.
  • James, W. D., T. G. Berger, D. M. Elston, and R. B. Odom. 2006. Andrews' Diseases of the Skin: Clinical Dermatology, 10th edition. Philadelphia: Saunders Elsevier. ISBN 0721629210.
  • McCormick, D. B. 2006. Vitamin B6 In B. A. Bowman, and R. M. Russell, (eds.), Present Knowledge in Nutrition, 9th edition, vol. 2. Washington, D.C.: International Life Sciences Institute. ISBN 9781578811984.
  • Mousain-Bosc, M., M. Roche, A. Polge, D. Pradal-Prat, J. Rapin, and J. P. Bali. 2006. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnes Res. 19(1): 46-52. PMID: 16846100.
  • National Institutes of Health (NIH), Office of Dietary Supplements. 2008. Dietary Supplement Fact Sheet: Vitamin B6. National Institutes of Health. Retrieved December 11, 2008.
  • Pfeiffer, S. I., J. Norton, L. Nelson, and S. Shott. 1995. Efficacy of vitamin B6 and magnesium in the treatment of autism: A methodology review and summary of outcomes. J Autism Dev Disord. 25(5):481-93. Comment in J Autism Dev Disord. 28(1998, issue 6): 580-1. Retrieved December 11, 2008.
  • Rowland, B., and R. J. Frey. 2005. Vitamin B6. In J. L. Longe, The Gale Encyclopedia of Alternative Medicine. Farmington Hills, Mich: Thomson/Gale. ISBN 0787693960.

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